Immunomodulation by oligonucleotides in tissue repair, regeneration, and cancer therapy

The field of immunomodulation and regenerative medicine has recently witnessed major interest in using oligonucleotide-based strategies to shape immune responses for therapeutic benefit. Oligonucleotides—including immunostimulatory, immunomodulatory, and gene-regulatory platforms—have emerged as powerful tools capable of fine-tuning both innate and adaptive immunity. These short nucleic acid sequences (DNA or RNA) act through mechanisms such as TLR9 activation (CpG ODNs), antisense inhibition, siRNA-mediated silencing, or engagement of other immune pathways. Despite considerable progress, a central challenge remains: how to precisely modulate immune activity to promote tissue repair and regeneration without triggering chronic inflammation, fibrosis, or tumor progression. The dual and context-dependent roles of the immune system—either supporting healing or contributing to tissue damage and tumor-promoting microenvironments—underscore the need for mechanistic understanding. Oligonucleotide therapeutics have shown promise in directing or suppressing specific immune processes, yet their full potential in coordinating immune-mediated repair and antitumor responses remains insufficiently defined.

This Research Topic aims to explore how oligonucleotide-based interventions can modulate immune responses to promote tissue repair, regeneration, and cancer control. The goal is to foster both mechanistic and translational studies that clarify how these nucleic acid platforms reprogram innate and adaptive immunity toward beneficial outcomes. Particular emphasis will be placed on studies integrating immunology, stem and progenitor cell biology, tumor microenvironment dynamics, and delivery system innovations. By identifying actionable immune targets and context-specific strategies, the Research Topic strives to advance immunomodulatory approaches that restore tissue homeostasis while preventing pathological remodeling and cancer progression.

To gather further insights into oligonucleotide-mediated immune modulation, we welcome articles addressing, but not limited to, the following themes:

- Molecular mechanisms of oligonucleotide-induced immune activation or regulation (e.g., TLRs, cGAS-STING, cytokine networks)
- Modulation of innate and adaptive immune cells in regenerative microenvironments
- Immune–stem/progenitor cell interactions and their role in tissue repair
- Impact of oligonucleotides on tumor microenvironment remodeling and antitumor immunity
- Mechanisms governing resolution of inflammation versus chronic or fibrotic responses
- Delivery systems and translational strategies for therapeutic oligonucleotides

We encourage submission of Original Research Articles, Brief Research Reports, Reviews, Mini-Reviews, and Perspectives. Both preclinical and clinical studies are welcome, particularly those combining mechanistic insight with therapeutic application across immunology, regenerative biology, oncology, and bioengineering.

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Classification
• Clinical Trial
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• ... View all formats

Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.

Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Classification
• Clinical Trial
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Policy and Practice Reviews
• Review
• Study Protocol
• Systematic Review
• Technology and Code

Keywords: Immunomodulation, Oligonucleotides, Tissue regeneration, Tumor microenvironment, Inflammation resolution, CpG oligodeoxynucleotides, TLR9 signaling, cGAS-STING pathway, Innate and adaptive immunity, Antisense and siRNA therapeutics

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.